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The effect of ionic strength was investigated at mildly acidic pH (5.5) in the presence of catalytic surfaces in the form of \u03b1-syn seeds or anionic lipid vesicles using thioflavin T fluorescence measurements. Similar trends were observed with both surfaces: increasing ionic strength reduced the rate of \u03b1-syn aggregation although the surfaces as well as \u03b1-syn have a net negative charge at pH 5.5. This anomalous salt dependence implies that short-range attractive electrostatic interactions are critical for secondary nucleation as well as heterogeneous primary nucleation. Such interactions were confirmed in Monte Carlo simulations of \u03b1-syn monomers interacting with surface-grafted C-terminal tails, and found to be weakened in the presence of salt. Thus, nucleation of \u03b1-syn aggregation depends critically on an attractive electrostatic component that is screened by salt to the extent that it outweighs the screening of the long-range repulsion between negatively charged monomers and negative surfaces. Interactions between the positively charged N-termini of \u03b1-syn monomers on the one hand, and the negatively C-termini of \u03b1-syn on fibrils or vesicles surfaces on the other hand, are thus critical for nucleation.<\/jats:p>","DOI":"10.1017\/qrd.2020.7","type":"journal-article","created":{"date-parts":[[2020,8,6]],"date-time":"2020-08-06T03:34:34Z","timestamp":1596684874000},"source":"Crossref","is-referenced-by-count":46,"title":["Anomalous Salt Dependence Reveals an Interplay of Attractive and Repulsive Electrostatic Interactions in \u03b1-synuclein Fibril 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